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Biomedical subjects

A Algra

Publications and source records attributed to A Algra.

At least 127 records · Page 7Linked to original sources
PubMed1999

[Clinical researchers and the pharmaceutical industry. Usefulness and need for an independent steering committee].

Clinical trials for testing the efficacy of new drugs in patients are subject to guidelines issued by the European Union ('Good clinical practice'). These guidelines address, in great detail, the relationship between the physician-investigator and the patient, and also that between the sponsoring industry and the physician-investigator (a deplorable exception being the financial arrangement). A major omission is the lack of safeguards for an appropriate and robust design of the study. This applies to the choice of measures of outcome and possible subgroups, interim analyses and stopping rules, entry and management of data, and the final analysis. It is therefore mandatory that the sponsoring industry allows full and early participation by senior clinicians in the design and execution of a clinical trial, through a steering committee.

Clinical Trials as Topic↗
PubMed1999

[Roaming through methodology. XII. Pragmatic and pathophysiologic trials: a question of goal formulation].

The design of clinical trials depends on the research question. In pragmatic trials the research question is: 'How do I treat patients with this disease?' In explanatory trials this question is: 'What is the mechanism of this new treatment?' Pragmatic trials are characterised by liberal patient selection, open treatment modalities corresponding with regular care, outcome measures considered from the patient's perspective and intention-to-treat analysis. In explanatory trials patient selection is strict and treatment is double-blind and pathophysiologically pure. Often proxy outcome measures are used and emphasis is on per protocol ('on treatment') analysis.

Clinical Trials as Topic↗
PubMed1999

[Secondary prevention after ischemic cerebral infarct. The ESPRIT Study: low dose anticoagulation, combined therapy with acetylsalicylic acid/dipyridamole or monotherapy with acetylsalicylic acid?].

The European and Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) is a randomised clinical trial in which patients with cerebral ischaemia of arterial origin will be randomised between oral anticoagulation (international normalized ratio (INR): 2.0-3.0), the combination of acetylsalicylic acid (in any dose between 30 and 325 mg per day) plus dipyridamole (400 mg daily) and acetylsalicylic acid only (in any dose between 30 and 325 mg per day). It is planned to enroll 4500 patients with a mean follow-up of three years. Primary outcome is the composite event of vascular death, stroke, myocardial infarction, or major bleeding complication; outcome assessment will be blinded. ESPRIT is an international, multi-center study in which 60-80 hospitals in the Netherlands and other countries in Europe and Australia will participate.

Anticoagulants↗
PubMed1999

Follow-up of idiopathic thunderclap headache in general practice.

Follow-up studies of idiopathic thunderclap headache (ITH) have found no subsequent subarachnoid hemorrhage (SAH) or other serious neurological disease, but the effect on life-style has not been studied. To assess the long-term outcome of patients with ITH in general practice we prospectively followed 93 patients with an episode of ITH during 1988-1993, of whom 77 were referred to hospital. ITH was defined as a sudden, unusually severe headache that started within 1 min, lasted at least 1 h, and for which no underlying cause was found. These patients were treated in 252 general practices. Outcome measures were subsequent SAH, subsequent headaches, absence from work, and diminished daily functioning. Patients were followed up by their general practitioner for a median of 5 years (range 1-10). Three patients died, all from non-neurological diseases. No subsequent SAH was diagnosed in any of the 93 patients. Recurrent attacks of ITH occurred in 8 patients, and 13 developed new tension headache or migraine. Absence from work because of headache was recorded in 11 patients, and in the overall group 6 patients were dependent on welfare. In only one-half of patients (n=52) did the general practitioner judge the level of daily functioning to be similar to that before the index episode of ITH. Thus, although no episodes of SAH occurred after ITH during long-term follow-up, one-half of patients with ITH had a lower level of daily functioning, and one-eighth had reduced working capacity, specifically because of headache.

Absenteeism↗
PubMed1999

How do general practitioners diagnose and manage patients with transient monocular loss of vision of sudden onset?

Symptoms of transient loss of vision in one eye differ widely. They may have different causes and therefore carry a different prognosis. We studied the influence of differences between characteristics of transient monocular blindness on the diagnosis and management by general practitioners (GPs). A postal questionnaire, was sent to 1600 GPs in The Netherlands along with four case vignettes describing a case history of a 56-year-old man with transient monocular disturbances of vision of sudden onset. We introduced random permutations in the following four elements of the history: partial or complete visual field involved, blurring or blacking out of vision, attacks lasting minutes or hours, and patients having covered either eye during the attack or not. Respondents were asked about the probable diagnosis and the preferred management. For each of the 16 permutations about 50 responses were obtained (overall response rate 54%). Ischemic transient monocular blindness (ITMB) was chosen as the most likely diagnosis in 49%. In 12% primary ocular disease was suspected. Involvement of the complete visual field, blacking out of vision, and short attacks were identified as independent predictors of a diagnosis of ITMB. A diagnosis of ITMB would have resulted in referral to a specialist in 72% of patients. Antithrombotic treatment would have been initiated in only 36% of ITMB patients. GPs consider brief attacks with complete blacking out of vision most typical for retinal ischemia. They refer only three-quarters of patients with probable ITMB to a specialist and start antithrombotic medication in only one-third of these patients. Therefore further education with regard to transient monocular blindness is needed.

Amaurosis Fugax↗
PubMed1999

Common carotid intima-media thickness in patients with peripheral arterial disease or abdominal aortic aneurysm: the SMART study. Second Manifestations of ARTerial disease.

Evidence is emerging that the contribution of atherosclerosis to the development of abdominal aortic aneurysm may differ from that of other manifestations of arterial disease. B-mode ultrasound may be helpful in understanding the characteristics and factors that contribute to the development of different manifestations of arterial disease. We examined whether there is a difference in common carotid intima-media thickness (IMT), an indicator of generalized atherosclerosis, in patients with peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA). IMT of the left and right common carotid artery was measured in the first 172 patients (123 PAD and 49 AAA) enrolled in the Second Manifestations of ARTerial disease (SMART) study, a cohort study among patients with a manifestation of atherosclerotic vascular disease or risk factors for atherosclerosis. Mean IMT was 0.98 +/- 0.34 mm in patients with PAD and 0.91 +/- 0.20 mm in patients with AAA, with an age and sex adjusted mean difference of 0.18 mm (95% CI 0.08; 0.28). After additional adjustments for cardiovascular risk factors, the difference remained 0.11 mm (95% Cl 0.01; 0.21). Common carotid IMT in patients with AAA is on average smaller than in patients with PAD, independent of other determinants of IMT. These findings support the view that the development of AAA cannot completely be explained by atherosclerosis and is in part due to other pathophysiological mechanisms.

Aged↗
PubMed1999

Which manufacturing characteristics are predictors of outlet strut fracture in large sixty-degree Björk-Shiley convexo-concave mitral valves? The Björk-Shiley Study Group.

BACKGROUND: Identification of predictors of outlet strut fracture is important for recipients of large (>/=29 mm) 60-degree Björk-Shiley convexo-concave mitral valves when it comes to decision making on prophylactic explantation. An association between the manufacturing process of Björk-Shiley convexo-concave valves and the risk of fracture has been suggested. OBJECTIVE: The aim of this study was to determine which items from the manufacturing records, in addition to known risk factors, were predictive of fracture of large 60-degree Björk-Shiley convexo-concave mitral valves. METHODS: All Dutch recipients (n = 2264) of Björk-Shiley convexo-concave valves were followed up until fracture, death, reoperation, or end of the study (July 1, 1996). Information was abstracted from the manufacturing records of large 60-degree Björk-Shiley convexo- concave mitral valves (n = 655) in Dutch recipients and included items that described the manufacturing process and items for which an association with strut fracture had been suggested. Manufacturing records were available for 637 valves (97%), including 25 fractured valves. RESULTS: Multivariate analysis identified age at implantation (hazard ratio 0.95, 95% confidence interval 0.93-0.97), lot size (<175 valves versus >/=175 valves; hazard ratio 6.6, 95% confidence interval 2.2-20.1), number of hook deflection tests performed (0 or 1 versus >/=2; hazard ratio 4.7, 95% confidence interval 1.4-16.2), number of disks that were used (1 versus >/=2; hazard ratio 5.9, 95% confidence interval 1.9-18.5), and lot fracture percentage (hazard ratio 1.6, 95% confidence interval 1.4-1. 8) as independent predictors of fracture. Although the added predictive value of a model with these 5 variables was sizable compared with a model containing age only, it was only slightly better than a model with age, lot size, and lot fracture percentage. CONCLUSION: If the serial number of a large 60-degree Björk-Shiley convexo-concave mitral valve is known, manufacturing information can add significantly to the prediction of fracture. Information on lot size and lot fracture percentage should be made available to clinicians for risk assessment of prophylactic explantation.

Equipment Failure Analysis↗
PubMed1999

Carotid artery stenosis in patients with peripheral arterial disease: the SMART study. SMART study group.

PURPOSE: The prevalence of asymptomatic internal carotid artery stenosis (ICAS) in patients with peripheral arterial disease (PAD) and characteristics that are associated with ICAS were studied. METHODS: We used data from the first 600 patients enrolled in the Second Manifestations of ARTerial disease (SMART) study, a single-center, prospective cohort study among patients referred with a manifestation of cardiovascular disease, diabetes mellitus, hypertension, or hyperlipidemia. Included in the analysis were 162 patients with PAD or a history of PAD, who were not known to have ICAS at the time of referral and who had no history of cerebrovascular symptoms or previous carotid endarterectomy. ICAS was detected with duplex scanning and defined as a peak systolic velocity more than 150 cm/s (diameter reduction 50% or higher) on at least one side. Cardiovascular risk factors were measured. Logistic regression analysis was performed to investigate associations between these characteristics and ICAS. RESULTS: The prevalence of previously unknown ICAS was 14%. A patient age of 67 years or older, body weight of 68 kg or less, and diastolic blood pressure of 75 mm Hg or lower were independently associated with ICAS. The Prevalence Of Icas In Patients With One Of These Characteristics (38% Of The Patients) Was 8%, In Those With Two Characteristics (21% Of The Patients) Was 32%, And In Those With Three Characteristics (6% Of The Patients) Was 50%. CONCLUSIONS: The prevalence of ICAS increases as much as 50% in patients who have PAD and the risk indicators of an age of 67 years or older, a body weight of 68 kg or less, and a diastolic blood pressure of 75 mm Hg or lower, and, therefore, these characteristics may be used as a means of increasing the likelihood of detecting ICAS.

Age Factors↗
PubMed1999

Systematic review of randomized controlled trials of aspirin and oral anticoagulants in the prevention of graft occlusion and ischemic events after infrainguinal bypass surgery.

PURPOSE: We sought to determine the efficacy of antiplatelet therapy and oral anticoagulants in maintaining graft patency and preventing ischemic complications in patients after infrainguinal bypass surgery. METHODS: We performed a meta-analysis of randomized controlled trials of aspirin with or without other antiplatelet therapy and oral anticoagulants after infrainguinal bypass surgery. Outcome measures studied were graft occlusion, stroke, myocardial infarction, vascular and total mortality, and the composite outcome of stroke, myocardial infarction, and vascular mortality. RESULTS: Five trials of antiplatelet therapy versus placebo were included. The relative risk (RR) for occlusion was 0.78 (95% CI, 0.64-0.95). For prevention of stroke, myocardial infarction, and death, and for the composite outcome, no significant effect was measured. Only one trial of oral anticoagulants versus control treatment was included. The RR for occlusion was 0.55 (95% CI, 0.30-0.99), and that for amputation was 0.30 (95% CI, 0.10-0.87). The mortality rate did not differ significantly between the groups. One trial of oral anticoagulant therapy plus aspirin versus aspirin alone in high-risk patients was included. The RR for occlusion was 0.38 (95% CI, 0.15-0. 95). There were no significant differences for prevention of amputation, myocardial infarction, and death between the groups. CONCLUSION: Antiplatelet therapy and oral anticoagulants reduce the risk of graft occlusion. Oral anticoagulant therapy appears to be the more effective treatment in high-risk patients. Data on the reduction of the risk of stroke, myocardial infarction, and death are inconclusive. Evidence for the beneficial effects of antiplatelet and oral anticoagulant therapy after infrainguinal bypass surgery is based on a small number of trials only. There is no proof as to which modality is the most effective in the prevention of graft occlusion and ischemic events in patients after infrainguinal bypass surgery, which is reason for a randomized comparison of aspirin with oral anticoagulants.

Administration, Oral↗
PubMed1999

Quality of life after infrainguinal bypass grafting surgery. Dutch Bypass Oral Anticoagulants or Aspirin (BOA) Study Group.

PURPOSE: The purpose of this study was to compare quality of life in patients with and without various ischemic complications after infrainguinal bypass grafting surgery for occlusive vascular disease. METHODS: A sample of patients (n = 746) randomized in the Dutch BOA study (n = 2645), a multicenter trial that compared the effectiveness of oral anticoagulant therapy with aspirin in the prevention of infrainguinal bypass graft occlusions, was entered in this study. On the basis of clinical outcomes of the trial, the patients were grouped as follows: patients with patent grafts (n = 409); patients with nontreated graft occlusions, subdivided into an asymptomatic group (n = 32) and a symptomatic group (n = 65); patients with subsequent revascularizations (n = 194); patients with amputations (n = 36); and patients with failed secondary revascularizations followed by secondary amputation (n = 38). In case an outcome event occurred, the patients were regrouped accordingly. Every half year, the patients completed a Short Form-36 and a EuroQol questionnaire. A multilevel model was used for repeated measure analysis. RESULTS: The mean follow-up time was 21 months. The quality of life in patients with nontreated asymptomatic occlusions was roughly similar to the quality of life in patients with patent grafts. Patients with symptomatic nontreated occlusions had the lowest outcome with regard to pain as compared with the other groups. Furthermore, physical and social functioning was lower for these patients than for patients with patent grafts. Revascularizations, successful or not, negatively affected pain, social functioning, and physical and emotional role. After successful revascularization, some improvement was observed in pain, physical and social functioning, and general and mental health as compared with the group with nontreated symptomatic occlusions. Amputation deteriorated physical functioning strikingly, especially after failed secondary revascularization. These patients also had the lowest scores of all the groups in the dimensions of social functioning, physical and emotional role, and mental health. EuroQol score showed deterioration of quality of life after all events, except for asymptomatic occlusions. The same patterns emerged if we stratified our analysis according to the indication for the initial operation: claudication or limb salvage. Quality of life was constant over time in all the groups in the observed period. CONCLUSION: Quality of life in patients with asymptomatic occluded grafts is similar to quality of life in patients with patent grafts. Revascularization of symptomatic occluded grafts improves quality of life to a certain extent. Amputation, in particular after failed secondary revascularization, seemed to be the lowest possible outcome. The results of the Short Form-36 and EuroQol measurements were in line with the clinical expectations. The association of disease severity with scores on the instruments supports the construct validity of these outcome measures for an objective assessment of quality of life in controlled studies.

Aged↗
PubMed1999

Second manifestations of ARTerial disease (SMART) study: rationale and design.

The Second Manifestations of ARTerial disease (SMART) study is a single-centre prospective cohort study among patients, newly referred to the hospital with (1) clinically manifest atherosclerotic vessel disease, or (2) marked risk factors for atherosclerosis. The first objectives of the SMART study are to determine the prevalence of concomitant arterial disease at other sites, and risk factors in patients presenting with a manifestation of arterial disease or vascular risk factor and to study the incidence of future cardiovascular events and its predictors in these high-risk patients. At least 1000 patients, aged 18 to 80 years, will undergo baseline examinations, including a questionnaire on cardiovascular disease, height, weight and blood pressure measurements, blood tests for glucose, lipids, creatinine and homocysteine, urinary tests for microproteinuria, resting twelve-lead electrocardiogram, ultrasound scanning of the abdominal aorta, kidneys and the carotid arteries, measurements of common carotid intima-media thickness and arterial stiffness, and a treadmill test to assess atherosclerosis of the leg arteries. Abnormal findings are reported to the treating specialist and general practitioner with a treatment suggestion according to current practice guidelines. Recruitment and baseline examinations began in September 1996. All cohort members will be followed for clinical cardiovascular events for a minimum of three years. In the scope of secondary prevention, the study is expected to support the design of solid based screening and treatment programmes and evidence-based cardiovascular medicine to reduce morbidity and mortality, and improve quality of life, in high-risk patients.

Adolescent↗
PubMed1999

Intensive lipid-lowering strategy in patients with diabetes mellitus.

AIMS: To assess the feasibility of an intensive lipid-lowering strategy in diabetic subjects pursuing target plasma lipid levels. METHODS: Patients with diabetes mellitus (DM), Type 1 or 2, with plasma lipid levels exceeding target values (LDL-cholesterol <2.6 mmol/l, triglycerides < 1.7 mmol/l, HDL-cholesterol > 0.9 mmol/l for men and > 1.1 mmol/l for women) were eligible. After 6-12 weeks of diet and glycaemic control, lipid-lowering medication (simvastatin/gemfibrozil/acipimox) was prescribed in steps of incremental dosages and combinations for 30 weeks. RESULTS: Of all eligible clinic patients, 25% initially responded and finally 12% were entered. Thirty-six patients with Type 1 and 59 with Type 2 DM were studied. Mean baseline lipid levels in Type 1 and Type 2 diabetic subjects were: LDL-cholesterol 3.6 and 3.7 mmol/l, triglycerides 1.7 and 2.2 mmol/l, HDL-cholesterol for men 1.1 and 1.0 mmol/l, and for women 1.4 and 1.2 mmol/l, respectively. All three target values were reached in 66% of the patients. LDL-cholesterol was reduced by 1.2 mmol/l in Type 1 and 1.3 mmol/l in Type 2 diabetic patients and triglycerides by 0.7 mmol/l and 1.1 mmol/l, respectively. HDL-cholesterol increased by 0.15 mmol/l and 0.34 mmol/l in men and women with Type 1 diabetes mellitus, respectively. The cholesterol-triglyceride ratio decreased significantly in VLDL in Type 1 diabetes and in IDL in Type 2 diabetes and increased significantly in HDL in Type 2 DM. CONCLUSIONS: A minority of subjects eligible for intensive lipid lowering agreed to participate in a feasibility study, suggesting a potentially large compliance problem for a general lipid-lowering programme in a diabetes clinic. Nevertheless, intensive lipid lowering with drug combinations can attain the recommended target lipid levels in 66% of subjects with diabetes. With this strategy the plasma lipoprotein composition shifts towards a less atherogenic profile. Subjects with diabetes should therefore receive lipid-lowering therapy tailored to reach target levels, rather than standard dosages, in order to reduce atherogenic risk.

Adult↗
PubMed1999

The myth of the in situ graft: superiority in infrainguinal bypass surgery?

OBJECTIVES: to compare the clinical outcome of in situ and reversed bypass grafting. DESIGN: multicentre, prospective, non-randomised study. PATIENTS AND METHODS: five-hundred patients with an in situ graft and 955 patients with a reversed graft were compared regarding graft occlusion, the need for graft revision, and limb salvage. RESULTS: two-year assisted primary patency of femoropopliteal bypass procedures was 82% for in situ and 82% for reversed grafts. The corresponding hazard ratio (HR) for occlusion was 1.27 (95% CI 0. 91-1.77). The 2-year assisted primary patency of femorocrural bypass procedures was 69% for in situ vs. 70% for reversed grafts. The corresponding HR was 1.13 (95% CI 0.73-1.75). Adjustment for relevant baseline variables did not change the results. More reinterventions were needed to maintain integrity and patency of the in situ graft especially in crural bypasses. No differences in limb salvage rates were seen. CONCLUSIONS: reversed and in situ vein grafts have similar patency and limb salvage rates for both femoropopliteal and femorocrural bypass procedures. The in situ graft needs more secondary interventions.

Aged↗